scholarly journals Complement C3 and Risk of Diabetic Microvascular Disease: A Cohort Study of 95202 Individuals from the General Population

2018 ◽  
Vol 64 (7) ◽  
pp. 1113-1124 ◽  
Author(s):  
Katrine Laura Rasmussen ◽  
Børge Grønne Nordestgaard ◽  
Sune Fallgaard Nielsen
Keyword(s):  
Diabetic Retinopathy ◽  
General Population ◽  
Microvascular Disease ◽  
Complement C3 ◽  
General Population Study ◽  
Hazard Ratios ◽  
Genome Wide ◽  
Heart Study ◽  
Increased Risk ◽  
High Concentrations

Abstract BACKGROUND Whether the complement system is involved in the development of diabetic microvascular disease is unknown. We tested the hypothesis that high concentrations of complement C3 are associated with increased risk of diabetic retinopathy, nephropathy, and neuropathy in individuals from the general population. METHODS We studied 95202 individuals from the general population with baseline measurements of complement C3, genotyped for rs1065489, rs429608, and rs448260 determining concentrations of complement C3, and enrolled in the Copenhagen General Population Study from 2003 through 2013, following them until April 10, 2013. Rs1065489, rs429608, and rs448260 were identified with genome-wide association scans in 3752 individuals from the Copenhagen City Heart Study. RESULTS The cumulative incidence was increased from the lowest tertile to the highest tertile of complement C3 for diabetic retinopathy (log-rank trend, P = 1 × 10−20), nephropathy (P = 7 × 10−15), and neuropathy (P = 5 × 10−10). Multifactorially adjusted hazard ratios for a 1 SD higher concentration of complement C3 were 1.87 (95% CI, 1.61–2.18) for diabetic retinopathy, 1.90 (1.62–2.23) for diabetic nephropathy, and 1.56 (1.29–1.89) for diabetic neuropathy. The multifactorially adjusted hazard ratio for individuals with the highest vs lowest tertile of complement C3 was 3.29 (1.78–6.07) for retinopathy, 2.71 (1.42–5.16) for nephropathy, and 2.40 (1.26–4.54) for neuropathy. CONCLUSIONS High baseline concentrations of complement C3 were associated with increased risk of diabetic retinopathy, nephropathy, and neuropathy in individuals from the general population. These epidemiological findings were substantiated by a Mendelian randomization approach, potentially indicating causality.

Increased Risk for Other Cancers in Addition to Breast Cancer for CHEK2*1100delC Heterozygotes Estimated From the Copenhagen General Population Study

2016 ◽  
Vol 34 (11) ◽  
pp. 1208-1216 ◽  
Author(s):  
Charlotte Näslund-Koch ◽  
Børge G. Nordestgaard ◽  
Stig E. Bojesen
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Population Study ◽  
Cell Cycle Checkpoint ◽  
Loss Of Function ◽  
General Population Study ◽  
Chek2 1100Delc ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Age And Sex

Purpose CHEK2 is a cell cycle checkpoint regulator, and the CHEK2*1100delC germline mutation leads to loss of function and increased breast cancer risk. It seems plausible that this mutation could also predispose to other cancers. Therefore, we tested the hypothesis that CHEK2*1100delC heterozygosity is associated with increased risk for other cancers in addition to breast cancer in the general population. Patients and Methods We examined 86,975 individuals from the Copenhagen General Population Study, recruited from 2003 through 2010. The participants completed a questionnaire on health and lifestyle, were examined physically, had blood drawn for DNA extraction, were tested for presence of CHEK2*1100delC using Taqman assays and sequencing, and were linked over 1943 through 2011 to the Danish Cancer Registry. Incidences and risks of individual cancer types, including breast cancer, were calculated using Kaplan-Meier estimates, Fine and Gray competing-risks regressions, and stratified analyses with interaction tests. Results Among 86,975 individuals, 670 (0.8%) were CHEK2*1100delC heterozygous, 2,442 developed breast cancer, and 6,635 developed other cancers. The age- and sex-adjusted hazard ratio for CHEK2*1100delC heterozygotes compared with noncarriers was 2.08 (95% CI, 1.51 to 2.85) for breast cancer and 1.45 (95% CI, 1.15 to 1.82) for other cancers. When stratifying for sex, the age-adjusted hazard ratios for other cancers were 1.54 (95% CI, 1.08 to 2.18) for women and 1.37 (95% CI, 1.01 to 1.85) for men (sex difference: P = .63). For CHEK2*1100delC heterozygotes compared with noncarriers, the age- and sex-adjusted hazard ratios were 5.76 (95% CI, 2.12 to 15.6) for stomach cancer, 3.61 (95% CI, 1.33 to 9.79) for kidney cancer, 3.45 (95% CI, 1.09 to 10.9) for sarcoma, and 1.60 (95% CI, 1.00 to 2.56) for prostate cancer. Conclusion CHEK2*1100delC heterozygosity is associated with 15% to 82% increased risk for at least some cancers in addition to breast cancer. This information may be useful in clinical counseling of patients with this loss-of-function mutation.

scholarly journals Low-Grade Inflammation in the Association between Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis: A Study of More Than 115000 Individuals from the General Population

2019 ◽  
Vol 65 (2) ◽  
pp. 321-332 ◽  
Author(s):  
Signe E J Hansen ◽  
Christian M Madsen ◽  
Anette Varbo ◽  
Børge G Nordestgaard
Keyword(s):  
Acute Pancreatitis ◽  
General Population ◽  
Low Grade ◽  
General Population Study ◽  
Reactive Protein ◽  
Hazard Ratios ◽  
Heart Study ◽  
Blood Leukocyte ◽  
Low Grade Inflammation ◽  
Multivariable Adjustment

Abstract BACKGROUND How mild-to-moderate hypertriglyceridemia (2–10 mmol/L; 177–886 mg/dL) potentially causes acute pancreatitis is unknown; however, cellular studies indicate that inflammation might be a driver of disease progression. We tested the hypotheses that (a) mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and that (b) the association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis depends on low-grade inflammation. METHODS From the Copenhagen General Population Study and the Copenhagen City Heart Study, 117865 men and women 20–100+ years of age with measurements of nonfasting plasma triglycerides at baseline were followed prospectively for development of acute pancreatitis. RESULTS After multivariable adjustment, a 1 mmol/L (89 mg/dL) higher nonfasting triglyceride concentration was associated with 17% (95% CI, 16%–18%, P = 3 × 10−17) higher plasma C-reactive protein (CRP) and a 4.2% (4.0%–4.4%, P = 6 × 10−17) higher blood leukocyte count. Higher concentrations of nonfasting triglycerides were associated almost linearly with higher risk of acute pancreatitis (P for trend = 5 × 10−6), with hazard ratios of 1.5 (95% CI, 0.9–2.5), 2.0 (95% CI, 1.1–3.6), 2.2 (95% CI, 1.0–4.7), 4.2 (95% CI, 1.6–11.5), and 7.7 (95% CI, 3.0–19.8) in individuals with nonfasting triglycerides of 1.00–1.99 mmol/L (89–176 mg/dL; 46% of the population), 2.00–2.99 mmol/L (177–265 mg/dL; 17%), 3.00–3.99 mmol/L (266–353 mg/dL; 6%), 4.00–4.99 mmol/L (354–442 mg/dL; 2%), and ≥5mmol/L(443 mg/dL; 2%), respectively, vs individuals with <1 mmol/L (89 mg/dL; 27%). The association with risk of acute pancreatitis appeared more pronounced in individuals with CRP of ≥1.39 mg/L (P for trend = 0.001) and leukocytes of ≥7 × 109/L (P = 2 × 10−4) than in those with CRP <1.39 mg/L (P = 0.03) and leukocytes <7 × 109/L (P = 0.04); however, there was no formal evidence of statistical interaction (P = 0.38 for CRP and P = 0.41 for leukocytes). CONCLUSIONS Mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and higher risk of acute pancreatitis. The association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis is possibly partly mediated by low-grade inflammation.

scholarly journals Serum Soluble CD163 Predicts Risk of Type 2 Diabetes in the General Population

2011 ◽  
Vol 57 (2) ◽  
pp. 291-297 ◽  
Author(s):  
Holger J Møller ◽  
Ruth Frikke-Schmidt ◽  
Søren K Moestrup ◽  
Børge G Nordestgaard ◽  
Anne Tybjærg-Hansen
Keyword(s):  
Type 2 Diabetes ◽  
General Population ◽  
Low Grade ◽  
Reactive Protein ◽  
Soluble Cd163 ◽  
Hazard Ratios ◽  
Heart Study ◽  
Increased Risk ◽  
Study Participants

BACKGROUND Activation of adipose tissue macrophages with concomitant low-grade inflammation is believed to play a central role in the development of type 2 diabetes. We tested whether a new macrophage-derived biomarker, soluble CD163 (sCD163), identifies at-risk individuals before overt disease has developed. METHODS A prospective cohort study of 8849 study participants from the general population, the Copenhagen City Heart Study, was followed for 18 years for incidence of type 2 diabetes. Risk of disease was calculated according to age- and sex-adjusted percentile categories of serum sCD163 concentrations: 0%–33%, 34%–66%, 67%–90%, 91%–95%, and 96%–100%. RESULTS A total of 568 participants developed type 2 diabetes. The cumulative incidence increased with increasing baseline sCD163 (trend P < 0.001), and sCD163 was strongly associated with known risk factors such as physical inactivity, body mass index, C-reactive protein, and triglycerides (all P < 0.001). Multifactorially adjusted hazard ratios for type 2 diabetes were 1.4 (95% CI, 1.0–1.9), 2.4 (1.8–3.2), 3.8 (2.6–5.5), and 5.2 (3.6–7.6) for categories 34%–66%, 67%–90%, 91%–95%, and 96%–100%, respectively, vs the 0%–33% category. In overweight men 50–70 and >70 years of age, serum sCD163 concentrations in the top 5% group predicted an absolute 10-year risk of type 2 diabetes of 29% and 36% vs 7% and 8% in the lowest percentile group. Equivalent values in women were 19% and 24% vs 4% and 5%. CONCLUSIONS Increased concentrations of sCD163 predict increased risk of type 2 diabetes in the general population and may be useful for identification of high-risk overweight individuals.

Abstract 3603: Extreme Lipoprotein(a) Levels Predict a 3–4 Fold Increase in Risk of Myocardial Infarction in the General Population

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Pia R Kamstrup ◽  
Marianne Benn ◽  
Anne Tybjćrg Hansen ◽  
Børge G Nordestgaard
Keyword(s):  
Myocardial Infarction ◽  
General Population ◽  
Fold Increase ◽  
Threshold Effect ◽  
Lipoprotein A ◽  
Hazard Ratios ◽  
Heart Study ◽  
Increased Risk ◽  
Increase In Risk

Background: Elevated lipoprotein(a) levels associate with increased risk of myocardial infarction in some, but not all studies. Limitations of previous studies include lack of risk estimates for extreme lipoprotein(a) levels, measurements in long-term frozen samples and no correction for regression dilution bias. We tested the hypothesis that extreme lipoprotein(a) levels predict myocardial infarction in the general population, measuring levels shortly after sampling and correcting for regression dilution bias. Methods and Results: We examined 9330 men and women from the Danish general population, The Copenhagen City Heart Study. During 10 years follow-up, 498 participants developed myocardial infarction. In women, multifactorially adjusted hazard ratios for myocardial infarction for elevated lipoprotein(a) levels were 1.1(95% confidence interval 0.6 –1.9) for 5–29 mg/dL, 1.7(1.0 –3.1) for 30 – 84 mg/dL, 2.6(1.2–5.9) for 85–119 mg/dL (>90 th percentile), and 3.6(1.7–7.7) for ≥120 mg/dL (>95 th percentile) versus levels <5 mg/dL (figure , p-values are test for trend of hazard ratios). Equivalent values in men were 1.5(0.9 –2.3), 1.6(1.0 –2.6), 2.6(1.2–5.5), and 3.7(1.7– 8.0). Conclusions: We observed a stepwise increase in risk of myocardial infarction with increasing levels of lipoprotein(a) in both genders, with no evidence of a threshold effect. Extreme lipoprotein(a) levels predict a 3– 4 fold increase in risk of myocardial infarction in the general population. Figure. Risk of myocardial infarction by levels of lipoprotein(a)

Elevated Plasma YKL-40 Predicts Increased Risk of Gastrointestinal Cancer and Decreased Survival After Any Cancer Diagnosis in the General Population

2009 ◽  
Vol 27 (4) ◽  
pp. 572-578 ◽  
Author(s):  
Julia S. Johansen ◽  
Stig E. Bojesen ◽  
Anne K. Mylin ◽  
Ruth Frikke-Schmidt ◽  
Paul A. Price ◽  
...  
Keyword(s):  
General Population ◽  
Cancer Diagnosis ◽  
Gastrointestinal Cancer ◽  
Early Death ◽  
Elevated Plasma ◽  
Hazard Ratios ◽  
Incident Cancer ◽  
Heart Study ◽  
Increased Risk ◽  
Risk Of Cancer

PurposeElevated plasma YKL-40 is a biomarker of poor prognosis in cancer patients. We tested the hypotheses that elevated plasma YKL-40 predicts risk of cancer as well as survival after a cancer diagnosis in the general population.Patients and MethodsA prospective cohort study of 8,899 subjects (20 to 95 years) from the Danish general population, the Copenhagen City Heart Study, observed for 11 years for cancer incidence and 14 years for death: 1,432 participants had a first incident cancer, 968 of these died. Hazard ratios (HRs) for cancer events and death after events according to plasma YKL-40 in sex and 10 years age percentile categories: 0% to 33%, 34% to 66%, 67% to 90%, 91% to 95%, and 96% to 100%.ResultsThe cumulative incidence of gastrointestinal cancer increased with increasing YKL-40 (trend P < .0001). Multifactorially adjusted HRs for gastrointestinal cancer were 1.0 (95% CI, 0.7 to 1.5) for YKL-40 in category 34% to 66%, 1.5 for 67% to 90% (95% CI, 1.0 to 2.3), 2.4 for 91% to 95%, (95% CI, 1.3 to 4.6), and 3.4 for 96% to 100% (95% CI, 1.9 to 6.1) versus YKL-40 category 0% to 33% (P < .0001). Participants with any cancer event and YKL-40 category 91% to 100% had a median survival time after the diagnosis of 1 year versus 4 years in participants with YKL-40 category 0% to 33% (P < .0001). Corresponding values for gastrointestinal cancer were 6 months versus 1 year (P = .007). Multifactorially adjusted HRs for early death were 1.8 (95% CI, 1.3 to 2.5; P < .0001) after any cancer and 2.4 (95% CI, 1.3 to 4.3; P = .005) after gastrointestinal cancer in participants with YKL-40 category 91% to 100% versus 0% to 33%.ConclusionIn the general population, elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis.

scholarly journals Increased Rheumatoid Factor and Deep Venous Thrombosis: 2 Cohort Studies of 54628 Individuals from the General Population

2015 ◽  
Vol 61 (2) ◽  
pp. 349-359 ◽  
Author(s):  
Christine L Meyer-Olesen ◽  
Sune F Nielsen ◽  
Børge G Nordestgaard
Keyword(s):  
General Population ◽  
Rheumatic Disease ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Rheumatoid Factor ◽  
General Population Study ◽  
Autoimmune Rheumatic Disease ◽  
Hazard Ratios ◽  
Increased Risk

Abstract BACKGROUND The risk of deep venous thrombosis is increased in patients with rheumatoid arthritis. We tested the hypothesis that increased concentrations of rheumatoid factor are associated with increased risk of deep venous thrombosis in individuals without autoimmune rheumatic disease in the general population. METHODS We included 54628 participants from the Copenhagen City Heart Study (1981–83) and the Copenhagen General Population Study (2004–12), all with a measured concentration of IgM rheumatoid factor and without autoimmune rheumatic disease or venous thromboembolism. The main outcome was incident deep venous thrombosis. There were no losses to follow-up. RESULTS During 368381 person-years, 670 individuals developed deep venous thrombosis. A rheumatoid factor concentration ≥ vs &lt;110 IU/mL showed the strongest association with deep venous thrombosis, with multivariable adjusted hazard ratios of 9.0 (95% CI 3.1–26) for 1-year follow-up, 4.3 (2.2–8.5) for 5-year follow-up, and 3.1 (1.7–5.6) for up to 32 years of follow-up. Compared with rheumatoid factor concentrations &lt;15 IU/mL, the multivariable adjusted hazard ratios for deep venous thrombosis during maximum follow-up were 1.3 (1.0–1.5) for 15–29 IU/mL, 1.7 (1.0–2.8) for 30–59 IU/mL, 2.4 (1.3–4.3) for 60–119 IU/mL, and 3.0 (1.6–5.6) for ≥120 IU/mL (trend P = 6 × 10−7). Results were similar in the 2 studies separately. Obese men and women age &gt;60 years with rheumatoid factor concentrations ≥120 IU/mL had 10% and 8% 5-year risk of deep venous thrombosis. CONCLUSIONS Increased rheumatoid factor in the general population was associated with up to 3-fold increased long-term risk and up to 9-fold increased 1-year risk of deep venous thrombosis.

scholarly journals Low high-density lipoprotein and increased risk of several cancers: 2 population-based cohort studies including 116,728 individuals

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Kasper Mønsted Pedersen ◽  
Yunus Çolak ◽  
Stig Egil Bojesen ◽  
Børge Grønne Nordestgaard
Keyword(s):  
General Population ◽  
Population Study ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Apolipoprotein A1 ◽  
General Population Study ◽  
Heart Study ◽  
Increased Risk ◽  
Low Hdl ◽  
Copenhagen City Heart Study

Abstract Background Increasing evidence suggests that high-density lipoprotein (HDL) may play a role in cancer development. We tested the hypothesis that low HDL levels are associated with increased risk of cancer. Methods Individuals from two population-based cohorts, the Copenhagen General Population Study (2003–2015, N = 107 341), and the Copenhagen City Heart Study (1991–1994, N = 9387) were followed prospectively until end of 2016 to assess low plasma HDL cholesterol and apolipoprotein A1 as risk factors for cancer using Cox proportional hazard regression. Results During up to 25 years follow-up, we observed 8748 cancers in the Copenhagen General Population Study and 2164 in the Copenhagen City Heart Study. In the Copenhagen General Population Study and compared to individuals with HDL cholesterol ≥ 2.0 mmol/L (≥ 77 mg/dL), multivariable adjusted hazard ratios (HRs) for any cancer were 1.13 (95% confidence interval 1.04–1.22) for individuals with HDL cholesterol of 1.5–1.99 mmol/L (58–77 mg/dL), 1.18 (1.08–1.30) for HDL cholesterol of 1.0–1.49 mmol/L (39–58 mg/dL), and 1.29 (1.12–1.48) for individuals with HDL cholesterol < 1.0 mmol/L (< 39 mg/dL). Correspondingly, compared to individuals with apolipoprotein A1 ≥ 190 mg/dL, HRs for any cancer were 1.06 (0.96–1.17) for individuals with apolipoprotein A1 of 160–189 mg/dL, 1.18 (1.07–1.30) for apolipoprotein A1 of 130–159 mg/dL, and 1.28 (1.13–1.46) for individuals with apolipoprotein A1 < 130 mg/dL. Among 27 cancer types, low HDL cholesterol and/or apolipoprotein A1 were associated with increased risk of multiple myeloma, myeloproliferative neoplasm, non-Hodgkin lymphoma, breast cancer, lung cancer, and nervous system cancer. Results were overall similar in women and men separately, and in the Copenhagen City Heart Study. Conclusions Low HDL levels were associated with increased risk of several cancers. Increased risk was most pronounced for hematological and nervous system cancer, and to a minor extent for breast and respiratory cancer.

scholarly journals Total and Cause-Specific Mortality by Moderately and Markedly Increased Ferritin Concentrations: General Population Study and Metaanalysis

2014 ◽  
Vol 60 (11) ◽  
pp. 1419-1428 ◽  
Author(s):  
Christina Ellervik ◽  
Jacob Louis Marott ◽  
Anne Tybjærg-Hansen ◽  
Peter Schnohr ◽  
Børge G Nordestgaard
Keyword(s):  
General Population ◽  
Total Mortality ◽  
Early Death ◽  
Premature Death ◽  
Population Based ◽  
General Population Study ◽  
Ferritin Concentration ◽  
Heart Study ◽  
Increased Risk ◽  
Specific Mortality

Abstract BACKGROUND Previous population-based studies of plasma ferritin concentration have not revealed a relationship with total mortality. We tested the possible association of increased ferritin concentrations with increased risk of total and cause-specific mortality in the general population. METHODS We examined total and cause-specific mortality according to baseline plasma ferritin concentrations in a Danish population–based study (the Copenhagen City Heart Study) of 8988 individuals, 6364 of whom died (median follow-up 23 years). We also included a metaanalysis of total mortality comprising population-based studies according to ferritin quartiles or tertiles. RESULTS Multifactorially adjusted hazard ratios (HRs) for total mortality for individuals with ferritin ≥200 vs &lt;200 μg/L were 1.1 (95% CI 1.1–1.2; P = 0.0008) overall, 1.1 (1.0–1.2; P = 0.02) in men, and 1.2 (1.0–1.3; P = 0.03) in women. Stepwise increasing concentrations of ferritin were associated with a stepwise increased risk of premature death overall (log rank, P = 2 × 10−22), with median survival of 55 years at ferritin concentrations ≥600 μg/L, 72 years at 400–599 μg/L, 76 years at 200–399 μg/L, and 79 years at ferritin &lt;200 μg/L. The corresponding HR for total overall mortality for ferritin ≥600 vs &lt;200 μg/L was 1.5 (1.2–1.8; P = 0.00008). Corresponding adjusted HRs for ferritin ≥600 vs &lt;200 μg/L were 1.6 (1.1–2.3; P = 0.01) for cancer mortality, 2.9 (1.7–5.0; P = 0.0001) for endocrinological mortality, and 1.5 (1.1–2.0; P = 0.01) for cardiovascular mortality. The metaanalysis random effects odds ratio for total mortality for ferritin upper vs reference quartile or tertile was 1.0 (0.9–1.1; P = 0.3) (P heterogeneity = 0.5). CONCLUSIONS Moderately to markedly increased ferritin concentrations represent a biological biomarker predictive of early death in a dose-dependent linear manner in the general population.

scholarly journals Association of Blood Eosinophil and Blood Neutrophil Counts with Asthma Exacerbations in the Copenhagen General Population Study

2017 ◽  
Vol 63 (4) ◽  
pp. 823-832 ◽  
Author(s):  
Signe Vedel-Krogh ◽  
Sune Fallgaard Nielsen ◽  
Peter Lange ◽  
Jørgen Vestbo ◽  
Børge Grønne Nordestgaard
Keyword(s):  
General Population ◽  
Disease Severity ◽  
Population Study ◽  
Blood Eosinophil ◽  
Blood Neutrophil ◽  
General Population Study ◽  
Asthma Exacerbations ◽  
Increased Risk ◽  
Blood Neutrophils ◽  
Eosinophil Counts

Abstract BACKGROUND Blood eosinophil count is a marker of eosinophilic airway inflammation and disease severity in asthma. However, blood neutrophil count might also be associated with disease severity. We tested the hypothesis that high blood eosinophil and neutrophil counts are both associated with the risk of asthma exacerbations among individuals with asthma from the general population. METHODS From the Copenhagen General Population Study with 81351 participants, we included 4838 with self-reported asthma. We recorded baseline blood eosinophil and neutrophil counts, and asthma exacerbations during follow-up in 2003–2011, defined as moderate (short-course treatment of prednisolone) or severe (hospitalization). RESULTS The multivariable-adjusted incidence rate ratios (IRRs) were 1.28 (95% CI, 1.06–1.55) for moderate exacerbations and 1.55 (1.20–2.00) for severe exacerbations for individuals with blood eosinophil counts &gt;0.29 × 109/L (highest tertile) vs individuals with blood eosinophil counts &lt;0.18 × 109/L (lowest tertile). For blood neutrophils, the multivariable-adjusted IRRs were 2.14 (1.74–2.63) for moderate exacerbations and 1.18 (0.89–1.55) for severe exacerbations for individuals with blood neutrophil counts &gt;4.85 × 109/L (highest tertile) vs individuals with blood neutrophil counts &lt;3.77 × 109/L (lowest tertile). Blood eosinophil and neutrophil counts interacted on moderate exacerbations (P = 3 × 10−4), but not on severe exacerbations. CONCLUSIONS High blood eosinophil counts are associated with an increased risk of both moderate and severe asthma exacerbations, while high blood neutrophil counts are associated with an increased risk of moderate, but not severe exacerbations.

Triglycerides and remnant cholesterol associated with risk of aortic valve stenosis: Mendelian randomization in the Copenhagen General Population Study

2020 ◽  
Vol 41 (24) ◽  
pp. 2288-2299 ◽  
Author(s):  
Morten Kaltoft ◽  
Anne Langsted ◽  
Børge G Nordestgaard
Keyword(s):  
Aortic Valve ◽  
General Population ◽  
Aortic Valve Stenosis ◽  
Population Study ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
General Population Study ◽  
Plasma Triglycerides ◽  
Increased Risk ◽  
Remnant Cholesterol

Abstract Aims We tested the hypothesis that higher levels of plasma triglycerides and remnant cholesterol are observationally and genetically associated with increased risk of aortic valve stenosis. Methods and results We included 108 559 individuals from the Copenhagen General Population Study. Plasma triglycerides, remnant cholesterol (total cholesterol minus low-density lipoprotein and high-density lipoprotein cholesterol), and 16 genetic variants causing such increased or decreased levels were determined. Incident aortic valve stenosis occurred in 1593 individuals. Observationally compared to individuals with triglycerides &lt;1 mmol/L (&lt;89 mg/dL), the multifactorially adjusted hazard ratio for aortic valve stenosis was 1.02 [95% confidence interval (CI) 0.87–1.19] for individuals with triglycerides of 1.0–1.9 mmol/L (89–176 mg/dL), 1.22 (1.02–1.46) for 2.0–2.9 mmol/L (177–265 mg/dL), 1.40 (1.11–1.77) for 3.0–3.9 mmol/L (266–353 mg/dL), 1.29 (0.88–1.90) for 4.0–4.9 mmol/L (354–442 mg/dL), and 1.52 (1.02–2.27) for individuals with triglycerides ≥5 mmol/L (≥443 mg/dL). By age 85, the cumulative incidence of aortic valve stenosis was 5.1% for individuals with plasma triglycerides &lt;2.0 mmol/L (77 mg/dL), 6.5% at 2.0–4.9 mmol/L (177–442 mg/dL), and 8.2% for individuals with plasma triglycerides ≥5.0 mmol/L (443 mg/dL). The corresponding values for remnant cholesterol categories were 4.8% for &lt;0.5 mmol/L (19 mg/dL), 5.6% for 0.5–1.4 mmol/L (19–57 mg/dL), and 7.4% for ≥1.5 mmol/L (58 mg/dL). Genetically, compared to individuals with allele score 13–16, odds ratios for aortic valve stenosis were 1.30 (95% CI 1.20–1.42; Δtriglycerides +12%; Δremnant cholesterol +11%) for allele score 17–18, 1.41 (1.31–1.52; +25%; +22%) for allele score 19–20, and 1.51 (1.22–1.86; +51%; +44%) for individuals with allele score 21–23. Conclusion Higher triglycerides and remnant cholesterol were observationally and genetically associated with increased risk of aortic valve stenosis.

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